This proposal studies the following areas: 1) The role of uterine PGE synthesis in controlling uteroplacental blood flow and arterial pressure during pregnancy. The hypothesis that the hypertension in toxemia is caused by decreased synthesis of PGE with increased sensitivity to angiotensin and norepinephrine developing will be investigated. 2) The effect of variable renal PGE synthesis on renal blood flow and cortical distribution of flow in conscious animals will be determined. The potential role of medullary PGE synthesis in regulating collecting tubule sensitivity to the hydro-osmotic effect of ADH will be studied in hypophysectomized dogs. Attempts will be made to separate the effect of various experimental maneuvers which alter ADH secretion through baroreceptors from the effect of these maneuvers on renal PGE synthesis by activation of either sympathetic nerves or the renin-angiotensin system. 3) A potential role for PGE synthesis in controlling sodium balance through a change in effective blood volume will be determined in hypokalemic animals. 4) Urinary PGE will be determined in hypertensive and normotensive humans with variable plasm renin. Factors controlling renal and arterial synthesis of PGE both in vivo and in vitro will be studied. 5) The mechanism of oliguria in dogs with hemoglobinuric renal failure will be investigated and factors which might control the severity of the lesion pathologically and clinically determined.